Dataset Information

Kinetics of Double-Stranded DNA Viremia After Allogeneic Hematopoietic Cell Transplantation.

ABSTRACT:

Background

Improved understanding of double-stranded DNA (dsDNA) virus kinetics after hematopoietic cell transplantation (HCT) would facilitate development of therapeutic strategies.

Methods

We tested weekly plasma samples from 404 patients through day 100 after allogeneic HCT for cytomegalovirus (CMV), human herpesvirus (HHV) 6A and 6B, BK polyomavirus (BKV), adenovirus (AdV), and Epstein-Barr virus (EBV) using quantitative polymerase chain reaction. Episodes lasting ≤1 week were defined as blips and >1 week as persistent. We described virus-specific kinetics, analyzed the association of virus area under the curve (AUC) with overall mortality, and identified risk factors for persistent episodes.

Results

We identified 428 episodes of CMV, 292 of BKV, 224 of HHV-6B, 46 of AdV, and 53 of EBV. CMV and BKV had the highest proportions of persistent episodes (68% and 80%, respectively). Detection and kinetics varied by virus. HHV-6B episodes reached maximum levels fastest and had the shortest intervals between detection and end-organ disease. End-organ disease occurred within 14 days of viremia in 68% of cases, generally during persistent episodes. For all viruses, higher viral load AUC increased risk for overall mortality through day 365, persistent episodes had higher viral load than blips, and higher first positive viral load significantly increased risk for persistent episodes. First viral load >2 log10 copies/mL (range, 2.04-3.06 per virus) had high specificity for persistent episodes.

Conclusions

Persistent high viral load dsDNA viremia episodes after allogeneic HCT predict mortality. Virus-specific kinetics can guide timing and thresholds for early intervention in studies of novel agents.

SUBMITTER: Hill JA

PROVIDER: S-EPMC5850428 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

Kinetics of Double-Stranded DNA Viremia After Allogeneic Hematopoietic Cell Transplantation.

Hill Joshua A JA Mayer Bryan T BT Xie Hu H Leisenring Wendy M WM Huang Meei-Li ML Stevens-Ayers Terry T Milano Filippo F Delaney Colleen C Jerome Keith R KR Zerr Danielle M DM Nichols Garrett G Boeckh Michael M Schiffer Joshua T JT

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20180101 3

<h4>Background</h4>Improved understanding of double-stranded DNA (dsDNA) virus kinetics after hematopoietic cell transplantation (HCT) would facilitate development of therapeutic strategies.<h4>Methods</h4>We tested weekly plasma samples from 404 patients through day 100 after allogeneic HCT for cytomegalovirus (CMV), human herpesvirus (HHV) 6A and 6B, BK polyomavirus (BKV), adenovirus (AdV), and Epstein-Barr virus (EBV) using quantitative polymerase chain reaction. Episodes lasting ≤1 week were ...[more]

PMID: 29020348

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Project description:Noninfectious pulmonary toxicity (NPT), a significant complication of allogeneic hematopoietic cell transplantation (alloHCT), includes idiopathic pneumonia syndrome (IPS), diffuse alveolar hemorrhage (DAH), and cryptogenic organizing pneumonia (COP), with an overall incidence ranging from 1% to 15% in different case series and a variable mortality rate. A registry study of the epidemiology and outcomes of NPT after alloHCT has not been conducted to date. The primary objective of the present study was to assess the incidence of and risk factors for IPS, DAH, and COP; the secondary objective was to assess overall survival (OS) in patients developing NPT. This retrospective study included adult patients who underwent alloHCT between 2008 and 2017 and reported to the Center for International Blood and Marrow Transplant Research. Multivariable Cox proportional hazards regression models were developed to identify the risk factors for development of NPT and for OS, by including pretransplantation clinical variables and time-dependent variables of neutrophil and platelet recovery, and acute graft-versus-host disease (GVHD) post-transplantation. This study included 21,574 adult patients, with a median age of 55 years. According to the HCT Comorbidity Index (HCT-CI), 24% of the patients had moderate pulmonary comorbidity and 15% had severe pulmonary comorbidity. The cumulative incidence of NPT at 1 year was 8.1% (95% confidence interval [CI], 7.7% to 8.5%). Individually, the 1-year cumulative incidences of IPS, DAH, and COP were 4.9% (95% CI, 4.7% to 5.2%), 2.1% (95% CI, 1.9% to 2.3%), and .7% (95% CI, .6% to .8%), respectively. Multivariable analysis showed that severe pulmonary comorbidity, grade II-IV acute GVHD, mismatched unrelated donor and cord blood transplantation, and HCT-CI score ≥1 significantly increased the risk of NPT. In contrast, alloHCT performed in 2014 or later, non-total body irradiation (TBI)- and TBI-based nonmyeloablative conditioning and platelet recovery were associated with a decreased risk. In a landmark analysis at day+100 post-transplantation, the risk of DAH was significantly lower in patients who had platelet recovery by day +100. Multivariable analysis for OS demonstrated that NPT significantly increased the mortality risk (hazard ratio, 4.2; P < .0001).

Dataset Information

Kinetics of Double-Stranded DNA Viremia After Allogeneic Hematopoietic Cell Transplantation.

Background

Methods

Results

Conclusions

Publications

Kinetics of Double-Stranded DNA Viremia After Allogeneic Hematopoietic Cell Transplantation.

Similar Datasets

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